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Definition: metabolic disorder from Cambridge Dictionary of Human Biology and Evolution

Disease or syndrome that affects normal metabolism; common examples are galactosemia, glycogen storage disease, fructose intolerance, lactose intolerance, phenylketonuria, and porphyria variegata. Aka metabolic disease. See nutritional disorder.

Summary Article: Metabolic Disorders
From Encyclopedia of Global Health

Metabolic disorders are disorders that affect production of energy within cells due to abnormal chemical reactions in the body.

Metabolism consists of anabolism (the build-up of substances) and catabolism (the breakdown of substances). Metabolism takes place via certain metabolic pathways catalysed by various enzymes. An alteration of enzyme function or a deficiency in enzyme levels result in metabolic disorders. The result is an inability to break down complex molecules from e.g. food and transform into energy, there may be a consequent build up of toxins. The largest classes of metabolic disorders include disorders of carbohydrate metabolism (e.g.s lactose intolerance, glycogen storage diseases); amino acid metbaolism (e.g.s phenylketonuria, maple syrup urine disease); fatty acid oxidation and mitochondrial metabolism disorders; porphyrin metabolism disorder; purine and pyrimidine metabolism disorder; steroid metabolism disorder; mitochondrial dysfunction; perizosmal dysfucntion and lysosoaml stroage disorders.

Most metabolic disorders are genetic in origin; however, some are acquired. These can be caused by a variety of sources including toxins, infections and diet. Hereditary disorders of metabolism include the condition phenylketonuria. This is an autosomal recessive disorder characterised by a deficiency of the enzyme phenylalanine hydroxylase; this enzyme metabolises phenylalanine to the amino acid tyrosine, enzyme deficiency hence leads to build up of phenylalanine which can be detected in urine. The disorder is characterised by the presence of mental retardation and seizures.

Another hereditary genetic metabolic disorder is lipidoses, this group of disorders are characterized by defects of the digestive system that impair the way the body uses fat from the diet. The various types of lipidoses include Fabry’s disease, Tay Sachs disease, Gaucher’s disease, Krabbe’s disease, Niemann-pick disease, Refsum’s disease and Wolman’s disease.

Fabry’s is an x-linked condition present in males. In this condition there is a defective gene which causes deficiency of the enzyme alpha-galactosidase A leading to accumulation of a glycolipid called globotriaosylceramide to accumulate within blood vessels and organs. The disease is characterised by pain and discomfort within the extremities. Patients may also have dark red-purple spots on the skin between the abdomen and knees.

Tay-Sachs disease is an autosomal recessive metabolic disorder commonly associated with Ashkenazi Jews. It is a fatal condition caused by a deficiency of the enzyme β-hexosaminidase A. This enzyme found in lysosomes normally breaks down a naturally occurring lipid called GM2-ganglioside. The enzyme deficiency leads to a toxic accumulation of GM2-ganglioside in the cells of the nervous system leading to neurodegeneration.

Gaucher’s disease is a lipid storage disease which occurs due to the deficiency of a lysosomal hydroxylase called glucerebrosidase resulting in deposition of glucocerebroside (glycosphingolipids important in muscle and cell membranes) in cells of the macrophage-monocyte system. The disease is characterized by various symptoms such as hepatomegaly (enlargement of the liver), splenomegaly (enlargement of the spleen), hypersplenism (increased activity of the spleen caused by e.g. anaemia), osteoporosis and yellow-brown skin pigmentation.

Krabbe’s disease is a rare, fatal disease caused by deficient activity of the lysosomal hydrolase galactosylceramide beta-galactosidase. This enzyme normally degrades galactosylceramide (found in myelin which insulates central nervous system), and beta-galactose–containing sphingolipids. The deficiency in enzyme causes build up of undigested fats leading to demyelination and degeneration of mental and motor skills.

Niemann-Pick disease is lipid storage disease causing lipid accumulation in organs such as spleen, liver, lungs and brain. The disease has 4 related types. Type A is the most common type; it is characterized by jaundice, hepatomegaly, and brain damage. Type B is characterised of hepatomegaly and splenomegaly with a sparing affect on the brain. In types of A and B insufficient activity of the enzyme sphingomyelinase leads to a toxic accumulation of sphingomyelin, a fatty substance present in every cell of the body. Types C and D are characterized by a defect that disrupts the transport of cholesterol between brain cells.

Refsum’s disease, a disease characterised by the accumulation of the fatty acid phytanic acid in plasma and tissues occurs due to a deficiency of phytanoyl-CoA hydroxylase (PhyH), a peroxisomal enzyme catalyzing the first step of phytanic acid alpha-oxidation. Phytanic acid is found in foods such as dairy products, white bread and rice.

This condition affects the nervous system, eyes, bones, and skin. Symptoms include retinitis pigmentosa (group of genetic eye conditions characterised by night blindness and tunnel vision), nystagmus (involuntary movement of the eyes which is usually from side to side), anosmia (lack of sense of smell) and loss of muscle coordination.

Wolman’s disease is a lipid storage disorder characterised by symptoms such as hepatomegaly, splenomegaly, steatorrhea (fecal matter is frothy, foul-smelling and floats due to a high fat content), abdominal distention and adrenal calcification that appears in the first weeks of life. It occurs due to the deficiency of lipase, an enzyme acid. This leads to the accumulation of lipids within the cells.

Metabolic disorders are characterized by a number of symptoms including hypertension, resistance to insulin, cholesterol abnormalities, obesity, and the increased risk of blood clotting. Additionally, these illnesses are often thought of in the context of endocrine disorders such as diabetes mellitus. Genetic diseases known as metabolic myopathies affect muscles; patients frequently develop fatigue, muscle pain, and weaker than normal muscle tissue because of a lack of energy.

There are many other metabolic disorders including Pompe’s disease, mucopolysaccharidoses, mitochondrial myopathies, Lesch-Nyhan syndrome, Farber’s disease, Barth syndrome and amyloidoses.

  • Endocrine Diseases (General); Genetic Disorders.

  • W. L. Nyhan; B. A. Barshop; O. T. Pinar, Atlas of Metabolic Diseases, 2nd ed. (Hodder Arnold, 2005).
  • Farhana Akter
    King’s College London
    Copyright © 2008 by SAGE Publications, Inc.

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